Signs of function in non-coding RNAs in mouse brain.

Over on his blog, Greg Laden points to some new work by John Mattick’s group on non-coding RNA expression in mouse brains. It’s interesting stuff, and worth a look. Please bear in mind as you do, however, that non-protein-coding but functional RNA is nothing new. Ribosomes are made of non-coding RNA, for one thing. Sadly, Greg seems to have bought into the distortions (several promoted by Mattick) about what people have said about non-coding DNA.

The “Junk DNA” story is largely a myth, as you probably already know. DNA does not have to code for one of the few tens of thousands of proteins or enzymes known for any given animal, for example, to have a function. We know that. But we actually don’t know a lot more than that, or more exactly, there is not a widely accepted dogma for the role of “non-coding DNA.” It does really seem that scientists assumed for too long that there was no function in the DNA.

As I have noted, people have been proposing functions for non-coding DNA since the beginning. As I noted in one of my first Genomicron posts,

Those who complain about a supposed unilateral neglect of potential functions for non-coding DNA simply have been reading the wrong literature. In fact, quite a lengthy list of proposed functions for non-coding DNA could be compiled (for an early version, see Bostock 1971). Examples include buffering against mutations (e.g., Comings 1972; Patrushev and Minkevich 2006) or retroviruses (e.g., Bremmerman 1987) or fluctuations in intracellular solute concentrations (Vinogradov 1998), serving as binding sites for regulatory molecules (Zuckerkandl 1981), facilitating recombination (e.g., Comings 1972; Gall 1981; Comeron 2001), inhibiting recombination (Zuckerkandl and Hennig 1995), influencing gene expression (Britten and Davidson 1969; Georgiev 1969; Nowak 1994; Zuckerkandl and Hennig 1995; Zuckerkandl 1997), increasing evolutionary flexibility (e.g., Britten and Davidson 1969, 1971; Jain 1980; reviewed critically in Doolittle 1982), maintaining chromosome structure and behaviour (e.g., Walker et al. 1969; Yunis and Yasmineh 1971; Bennett 1982; Zuckerkandl and Hennig 1995), coordingating genome function (Shapiro and von Sternberg 2005), and providing multiple copies of genes to be recruited when needed (Roels 1966).

I am not about to claim that the study hasn’t shown evidence of function for these non-coding regions. I think it’s quite interesting, and it wouldn’t surprise me if lots of non-coding RNA turned out to have a regulatory function. But let’s be realistic with this. The authors consider a “long” non-coding RNA transcript to be >200bp. So let’s just round up and say 1,000bp for convenience. They identified around 850 potentially functional sequences (and ~500 that do not show evidence of functional expression, at least in the brain) and estimate that there are 20,000 of them all told. 1,000bp x 20,000 = 20Mb. The mouse genome is about 3Gb. In other words, this study, even read generously, has identified possible function for 0.7% of the mouse genome.

In summary, cool research. Important question, neat result. But let’s not start the usual extrapolationfest that normally accompanies such publications.



11 comments to Signs of function in non-coding RNAs in mouse brain.

  • Greg Laden

    Don’t be sad, T. Ryan. But you should read more carefully. Perhaps I overstate when I say that “Junk” is a myth, but I also state that this is terra incognito.

    However, I will gladly add a link to your critique of this paper to my overview of it.

    Cheers,

    Happy Greg

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  • TR Gregory

    Dear Happy Greg,

    It’s the last line that turned my smile into a frown, because the claim that all scientists have ignored function is clearly false, but one that is made only too happily by anti-evolutionists. And some former gene-centric researchers.

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  • greg laden

    T:

    This is an interesting discussion, but not because of how it relates to Junk DNA.

    This is my response to both your comments and Larry Moran’s

    Cheers,

    G

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  • TR Gregory

    Hi Greg,

    I can only assume that your recent post is aimed mostly at Larry’s bit, as it seems only vaguely related to what I wrote.

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  • Greg Laden

    TRG: Yes, that is absolutely correct.

    I like Larry and is blog, but I think he likes to pick fights. I might regret having extended the courtesy of letting him know about this discussion, but I still hold out hope he will make a useful contribution to the discussion.

    I would like to see this discussion of “Junk DNA” develop in a more productive direction, with less vitriol and more discussion of what is important.

    GTL

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  • TR Gregory

    Hi Greg,

    I have been writing about what is important, without vitriol (which, I am disheartened to note, was not true of your post), for quite a while.

    What doesn’t help, I’m afraid, is the kind of blanket (and historically incorrect) statement you made in setting up your discussion.

    As I have clarified, that was all I was reacting to in terms of the original post and the article under discussion — the study itself and its observations are very interesting and well worth discussing, without the other hyperbole.

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  • Mike the Mad Biologist

    What I find disheartening (and I’m not saying this about you, but more generally) is the tendency to assert that only certain people (usually ‘ego’ in a particular conversation, to use a kinship term) are qualified, perhaps a better word is ‘allowed’ to comment on certain issues. There is a club, and if you are not in the club than please be quite. How annoying.

    My intention, in my original post, was to draw the contrast between what I perceive as a popular … and not formally defined … understanding of DNA, as a segue into a non committal exposition of a new paper exploring ncRNA.

    I’m reminded of a discussion that happened a while back about “what is a gene.” Definitions of a gene that attempted to restrict that term to sequences of DNA that code for proteins were resoundingly rejected on two grounds: Some DNA codes for molecules that are not proteins, and there are parts of the DNA that are not part of the transcription code but that are essential to expression. Furthermore, genome size might matter (I say “might” as a defense mechanism … I happen to think it does matter).

    I think my phrase ‘The “Junk DNA” story is largely a myth” has been widely read as “All the so-called Junk DNA has a function.” This is not what I meant. Had this been something other than a blog post I may have revised a couple of times and avoided any possibility of that misinterpretation.

    My statement “But we actually don’t know a lot more than that, or more exactly, there is not a widely accepted dogma for the role of “non-coding DNA.”” does not seem to be very supportive of any particular proposition of function in “the junk.”

    My statement “It does really seem that scientists assumed for too long that there was no function in the DNA. ” may well be a mis statement, or at least, it does not apply to all scientists, and I’m vague about when I mean by “for too long.”

    Let me tell you that being told (incorrectly) that I have “bought into the distortions” or that I have been “suckered by John Mattick” are not nice things to hear, as they are not too indirect ways of questioning my ability to reason, which is important to me, and they are also utterly inaccurate. If I have been vitriolic in my response, I deeply apologize, but I must also say that others may well have responded to what could be interpreted as a direct insult to one’s intelligence with substantially more vitriol.

    I do hope that further discussion of ncRNA ensues, as I’m not very interested in too much further discussion of Greg Laden’s inability to think exactly like others! I AM very interested in your further thoughtful and well informed analysis of the actual issue.

    Cheers,

    GTL

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  • greg laden

    OH, by the way, I am not Mike the Mad Biologist. I would like to explain why the above post seems to be written by Mike, but I don’t have time and it is not that interesting….

    Greg Laden, actual writer of the above post.

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  • TR Gregory

    Greg,

    I never said you couldn’t comment. One of my very first posts was about the bird genome size story (which, by the way, is based in no small part on my work), and I linked favourably to your comments about it.

    Please bear in mind that you made the claims about “junk DNA is a myth”, implied that it was turning out to be functional on the basis on new data, and that (if true) this would be a surprise to most biologists. These are incorrect statements, but they do follow what Mattick — an author of the paper you discussed — has said many times. I think my conclusion that you a) said something incorrect, and b) got this in part from Mattick, were logically sensible. Beyond that, there was no attack in my post about your comment, and I agreed that the paper is interesting.

    I have no problem with people making forays into my area of study, but they are held to the same expectation of getting the facts correct as anyone else.

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  • TR Gregory

    Let me tell you that being told (incorrectly) that I have “bought into the distortions” or that I have been “suckered by John Mattick” are not nice things to hear, as they are not too indirect ways of questioning my ability to reason, which is important to me, and they are also utterly inaccurate.

    Or, they could be based on a lack of familiarity with the literature, which is why I pasted in a list of examples that contradict what you suggested.

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  • TR Gregory

    My statement “But we actually don’t know a lot more than that, or more exactly, there is not a widely accepted dogma for the role of “non-coding DNA.”” does not seem to be very supportive of any particular proposition of function in “the junk.”

    I will admit that “there is not a widely accepted dogma for the role of non-coding DNA” was taken to imply that there was a priori reason to expect such a role and we just don’t know it yet.

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